Featured Research

from universities, journals, and other organizations

New Computational Model Allows For Better Understanding Of AIDS Drug

Date:
July 25, 2006
Source:
Virginia Tech
Summary:
Researchers at the Virginia Bioinformatics Institute (VBI) at Virginia Tech have developed a computational model that allows scientists to better understand the metabolism and toxicity of the HIV/AIDS drug zidovudine (azidothymidine, AZT).

Researchers at the Virginia Bioinformatics Institute at Virginia Tech have developed a computational model that allows scientists to better understand the metabolism and toxicity of the HIV/AIDS drug zidovudine (azidothymidine, AZT).

Related Articles


AZT is used successfully as part of Highly Active Anti-Retroviral Therapy (HAART) to control the level of the human immunodeficiency virus in HIV-infected individuals. However, long-term use of AZT may lead to side-effects in some patients. David Samuels and coworkers are interested in finding out whether the toxic side effects of AZT can eventually be minimized or even eliminated. For this purpose, they have been developing a detailed computational model that allows scientists to simulate the biochemical reactions that take place when AZT is metabolized in cells, including their mitochondria, under different metabolic conditions. Drugs like AZT may interfere with DNA replication in the mitochondria, the energy factories of our cells, and can lead to potentially fatal side effects in patients undergoing HAART treatment.

“HAART is one of the biggest success stories in modern medicine. The goal of our work is to help improve this successful treatment by understanding the toxic effects that AZT can have in some people. There are many different ways that AZT could possibly interfere with mitochondria to cause the toxic side-effects. Our job is to model these proposed toxicity mechanisms to see which ones could actually lead to the mitochondrial defects found in AIDS patients, ”said Dr Samuels, assistant professor at Virginia Bioinformatics Institute. “It is possible that no single mechanism is responsible for the toxicity, but that instead a combination of multiple effects is needed. That is the kind of problem that needs a systems biology approach.”

When AZT reaches a cell, it is subject to some of the same metabolic modifications or phosphorylation events that are encountered by the four naturally occurring deoxynucleosides, the building blocks used to make DNA. However, modified AZT molecules lack a specific chemical group (a hydroxyl group) that would allow DNA replication to continue. This results in premature termination of DNA synthesis. It is thought that the triphosphorylated form of AZT can enter the mitochondrial matrix, the inner core of the mitochondrion, and disrupt the replication of mitochondrial DNA by prematurely terminating DNA synthesis.

“We’re just starting our work. It is too early to say what the mechanism of mitochondrial toxicity of AZT is. The inhibition of deoxynucleoside metabolism is one possibility. The incorporation of AZT into mitochondrial DNA is another,” added Samuels. “The detailed computational model that we have developed should allow researchers to explore different hypotheses as to why AZT can lead to such debilitating side effects in some patients undergoing anti-retroviral treatment.”

This research is supported by National Institutes of Health grant DK070533.

The Virginia Bioinformatics Institute (VBI) at Virginia Tech has a research platform centered on understanding the “disease triangle” of host–pathogen–environment interactions in plants, humans and other animals. By successfully channeling innovation into transdisciplinary approaches that combine information technology and biology, researchers at VBI are addressing some of today’s key challenges in the biomedical, environmental and plant sciences.


Story Source:

The above story is based on materials provided by Virginia Tech. Note: Materials may be edited for content and length.


Cite This Page:

Virginia Tech. "New Computational Model Allows For Better Understanding Of AIDS Drug." ScienceDaily. ScienceDaily, 25 July 2006. <www.sciencedaily.com/releases/2006/07/060725074310.htm>.
Virginia Tech. (2006, July 25). New Computational Model Allows For Better Understanding Of AIDS Drug. ScienceDaily. Retrieved December 18, 2014 from www.sciencedaily.com/releases/2006/07/060725074310.htm
Virginia Tech. "New Computational Model Allows For Better Understanding Of AIDS Drug." ScienceDaily. www.sciencedaily.com/releases/2006/07/060725074310.htm (accessed December 18, 2014).

Share This


More From ScienceDaily



More Computers & Math News

Thursday, December 18, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Jaguar Unveils 360 Virtual Windshield Making Car Pillars Appear Transparent

Jaguar Unveils 360 Virtual Windshield Making Car Pillars Appear Transparent

Buzz60 (Dec. 17, 2014) Jaguar unveils a virtual 360 degree windshield that may be the most futuristic automotive development yet. Jen Markham explains. Video provided by Buzz60
Powered by NewsLook.com
BlackBerry Launches Classic Smartphone

BlackBerry Launches Classic Smartphone

AP (Dec. 17, 2014) BlackBerry is returning to its roots with a new smartphone called the Classic, featuring a traditional keyboard at a time when rival Apple and Android phones - and most smartphone customers - have embraced touch screens. (Dec. 17) Video provided by AP
Powered by NewsLook.com
The Future of Work, Skills & Careers in a Digital World-Dr. Tracy Wilen

The Future of Work, Skills & Careers in a Digital World-Dr. Tracy Wilen

Working Mother (Dec. 16, 2014) 2014 Worklife Congress Video provided by Working Mother
Powered by NewsLook.com
Tech Companies Make Holiday Shopping Easier Than Ever

Tech Companies Make Holiday Shopping Easier Than Ever

Newsy (Dec. 16, 2014) Innovative new services allow consumers to shop with their smartphones, split bills and even haggle. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Space & Time

Matter & Energy

Computers & Math

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins